What is the recommended antithrombotic regimen for a patient with ischemic stroke and atrial fibrillation (AF), considering the use of aspirin, clopidogrel, and apixaban?

Recommended Antithrombotic Regimen for Ischemic Stroke with Atrial Fibrillation

For patients with ischemic stroke and atrial fibrillation, oral anticoagulation with apixaban (or another DOAC) should be initiated without aspirin or clopidogrel for long-term secondary stroke prevention. 1, 2

Acute Phase Management (First 1-2 Weeks)

Initial Antiplatelet Therapy

• Start aspirin 160-325 mg within 48 hours of stroke onset as bridging therapy until therapeutic anticoagulation is achieved 1
• Aspirin serves only as temporary bridging and should be discontinued once anticoagulation reaches therapeutic levels 1

Timing of Anticoagulation Initiation

• Initiate oral anticoagulation within 1-2 weeks after stroke onset for most patients 1
• Earlier initiation (within days) can be considered for patients with:
  • Small infarct burden 1
  • No hemorrhage on brain imaging 1
• Delay anticoagulation beyond 2 weeks for patients with:
  • Extensive infarct burden 1
  • Significant hemorrhagic transformation on imaging 1

Long-Term Anticoagulation Strategy

Preferred Anticoagulant Choice

• Apixaban 5 mg twice daily is the preferred agent over warfarin for stroke prevention in AF 2, 3
• Reduce to apixaban 2.5 mg twice daily if patient has at least 2 of the following: 3
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Strong Evidence Against Antiplatelet Therapy

• Oral anticoagulation is strongly recommended over aspirin alone (Grade 1B) 1
• Oral anticoagulation is strongly recommended over aspirin plus clopidogrel combination (Grade 1B) 1
• Antiplatelet therapy provides only 22% stroke risk reduction compared to 62% with oral anticoagulation 2

Critical Management Principles

Discontinue Antiplatelet Therapy After Anticoagulation

• Stop aspirin and clopidogrel once therapeutic anticoagulation is established 2
• Continuing antiplatelet therapy with anticoagulation significantly increases bleeding risk without additional stroke prevention benefit 2
• The only exception is if the patient has a concurrent acute coronary syndrome or recent stenting requiring dual antiplatelet therapy 4

Why Not Triple Therapy?

• Triple therapy (apixaban + aspirin + clopidogrel) dramatically increases major bleeding risk without improving stroke prevention in AF patients 2, 4
• Aspirin increased major or clinically relevant non-major bleeding, particularly in patients without recent coronary events 4

Special Considerations

Renal Function Monitoring

• Assess renal function before initiating apixaban and at least annually 2, 5
• Apixaban requires dose adjustment based on renal function 1, 3
• For severe renal impairment (CrCl <15 mL/min) or dialysis, warfarin is preferred over DOACs 2, 5

Valvular Heart Disease

• For mitral stenosis, use warfarin instead of apixaban 2, 5
• For mechanical heart valves, use warfarin with target INR ≥2.5 5

Common Pitfalls to Avoid

• Never continue long-term aspirin or clopidogrel with oral anticoagulation in AF patients without concurrent coronary indications 2
• Never use antiplatelet monotherapy when oral anticoagulation is indicated (patient has had a stroke, giving them a CHA₂DS₂-VASc score ≥2) 1, 2
• Never discontinue anticoagulation after cardioversion or ablation if stroke risk factors persist 2, 5
• Never overestimate bleeding risk leading to inappropriate withholding of anticoagulation—the stroke risk far exceeds bleeding risk in this population 2, 5

Algorithm Summary

1. Day 0-2: Start aspirin 160-325 mg 1
2. Day 3-14: Initiate apixaban (timing based on infarct size and hemorrhage risk) 1
3. Upon therapeutic anticoagulation: Discontinue aspirin 1, 2
4. Long-term: Continue apixaban monotherapy indefinitely 1, 2